Gluten-sensitive enteropathy (GSE; VIM 607202) or celiac disease (CD; MIM 212750) has been well recognized as a public health concern for some time in Europe. During the last 10-15 years gluten sensitive enteropathy (GSE) has become better recognized in the United States as a serious, but under-diagnosed health problem, with recent estimates of its prevalence in the general U.S. population ranging from 1:135 to 1:250. The purpose of this pilot study is to demonstrate the presence of GSE in the Amish with the ultimate goal in a future application to identify susceptibility loci for GSE in this genetically homogenous population. The Old Order Amish can trace their ancestry to a limited number of founder couples who emigrated from Europe in the early 1700's. The deep pedigree structure, large families, longevity, and the homogeneous life-style of the Amish will be major advantages for genome-wide linkage and association analysis. GSE is a complex immunogenetic disorder due to intolerance to dietary prolamins found in wheat, barley, and rye. In genetically susceptible individuals, ingestion of the prolamins elicits an inflammatory injury to the small intestine with villous atrophy and consequent malabsorption. The clinical signs and symptoms range from overt to silent. Treatment with a life-long gluten-free diet (GFD) typically reverses the mucosal damage. The major histocompatibility complex class II alleles DQA1*0501 and DQB*0201 represent a major genetic association to the patho-physiology of GSE. The HLA-DQ2 allelic combination is found in >90% of celiac patients from northern Europe. However, the variable penetrance, 30%-50% concordance for GSE in HLA identical siblings, and near 100% concordance in monozygotic twins suggests a major patho-physiological role for additional gene loci. Approximately 1,200 individuals have been recruited and enrolled in the Amish Family Osteoporosis Study (AFOS). We propose to screen the existing AFOS serum and DNA samples for diagnostic biomarkers of CD in order to (1) demonstrate the presence of GSE in the Amish and (2) recruit additional family members around study subjects with positive GSE biomarker tests.